The goal of this competing continuation is to complete a 30-year longitudinal study of a stable population of cotton textile workers in Shanghai, China. This cohort has been evaluated for cotton dust and endotoxin exposure as well as pulmonary effects since 1981. This unique study remains the longest and largest prospective cohort study of textile workers to date, with an unusually high (> 80%) participation rate and a large proportion of non-smokers. To date, this study has enabled us to report dust and endotoxin-related pulmonary effects, including new insights on the effect of exposure cessation and the role of some candidate genes related to endotoxin exposure. However, scientific uncertainties remain. Specifically, for over five decades, controversy continues as to whether emphysema or chronic bronchitis is the basis of the observed airway obstruction. Prior autopsy studies on small numbers of deceased workers have been conflicting. With the advent of improved high resolution computed tomography (HRCT) since 2002, as well as validated automated techniques to quantify the degree of emphysema and airways disease present in an individual, this proposal represents an unusual opportunity to apply this innovative technology to this unique and well characterized cohort of cotton and silk textile workers. We propose to extend follow-up in our study to a 30 year sampling so that we may explore in vivo several data-intensive strategies to elucidate the biological processes involved in dust and endotoxin-related lung disease. Our first aim is to assess the relationship between respiratory health status and long term exposure to cotton dust and endotoxin, as well as evaluate the effect of removal of exposure in retired workers; our second aim is to perform HRCT of the chest in study cohort volunteers, both exposed and unexposed to dust/endotoxin and with/without respiratory disease to identify the structural basis for the observed lung impairment. Finally, in the third aim we will test additional candidate gene polymorphisms that may modulate the development of dust and endotoxin-related airways disease. Continued study of this unique cohort by our experienced group of investigators using a comprehensive and innovative approach will help us identify key biological basis underlying the development of occupationally-related airways disease from organic dust and endotoxin exposure. The study addresses respiratory disease in the health outcome cross-sectors portion of the NIOSH extramural program portfolio.